In the Beginning. . .or Icky Genesis Genetics

1In the beginning God created the heaven and the earth.2And the earth was without form, and void; and darkness was upon the face of the deep. And the Spirit of God moved upon the face of the waters. – Genesis 1:1-2 (King James Version – KJV)

And then he made humans, at least twice-ish[1]. Embarrassingly, he seemed to only make one family, which meant that when it came time for Adam and Eve’s son, Cain[2], to go looking for a bride, he was not going to go looking very far from home.

If you are not descended from a line of Egyptian pharaohs, now is the time to say “EWWW!” and start wondering why all of humanity doesn’t look like Cletus the Slack-Jawed Yokel.

According to the Book of Jubilees, (of which those who are not Eastern Orthodox Christians or ancient Jews may not have heard[3]) Cain married his sister, Awan. Kills his own brother and gets it on with his sister? Stay classy, Cain. Stay classy.

Unless you happen to be a dog breeder from 1924, you may realize that matings between close relatives is bad news. Or is it?

Despite this ignominious start, humanity does not seem to be burdened with the baleful, genetic consequences of inbreeding[4], unlike many “purebred” domestic critters. You might argue that this is merely an ancient myth. Boring. Or, you might suggest that a loving, but myopic, god miraculously tweaked the primordial Punnett Square to avoid any awkwardness. Boring and arbitrary.

And, unnecessary, if you take a look at the actual biology. To do so, we will first need to go beyond the social conception of inbreeding to get to the genetic definition and, then, examine why such inbreeding is generally considered harmful.

Matings between close relatives is frowned upon, although there is cultural variation in the definition of “close”[5]. Genetics uses a more rigorous definition, that is based on the concept of identity by descent. Two copies of a gene are identical by descent if they are both descendant copies from the same original DNA molecule encoding that particular version of the gene. For example:

At a random gene, your dad has the genotype Aa and your mom has the same genotype Aa. A and a are two different versions (alleles) of that gene. Bold type indicates which parent the copy is coming from (mom). A has the same sequence as A. You inherited A from dad and a from mom, giving you genotype Aa. Your sister is aa. Your a copy and your sibling’s a copy are identical by descent, because they both derived from your mother’s a copy. Your a copy and your sibling’s a copy are not identical by descent, even though they are the version of the gene, because they come from different copies. Yours comes from mom, hers from dad.

With that in mind, we can define inbreeding:

The measure is the coefficient of inbreeding, which is the probability that the two genes at any locus in an individual are identical by descent.

By this definition, how inbred would Cain and Awan’s kids have been? Well it depends on which creation story from Genesis we use. In the first, males and females are created simultaneously, individually, and in god’s image:

27So God created man in his own image, in the image of God created he him; male and female created he them. – Genesis 1:27 (KJV – creation of man & woman)

In the first story, both Adam and Eve are created from scratch. Their genes have no identity by descent. Therefore, the probability that the two copies of any given gene in Cain were identical by descent is zero; but, for his kids, the probability becomes 25%, because there is a 50:50 chance that Cain and Awan inherited the same copy of a gene from Adam.

In the second, god first creates man and, then, uses a rib from that man to create woman:

7And the LORD God formed man of the dust of the ground, and breathed into his nostrils the breath of life; and man became a living soul. – Genesis 2:7 (KJV – the creation of Adam)

21And the LORD God caused a deep sleep to fall upon Adam, and he slept: and he took one of his ribs, and closed up the flesh instead thereof; 22And the rib, which the LORD God had taken from man, made he a woman, and brought her unto the man. – Genesis 2:21-23 (KJV – the creation of Eve)

In this story, Eve appears to get all her genetic material from Adam[6] making all genes are identical by descent. Therefore, the probability that the two copies of any given gene in Cain’s kids were identical by descent is 100%.

The different myths give us quite a bit of range on our inbreeding estimates; but, it is not identity by descent alone that makes inbreeding bad for you.

What is it about inbreeding that causes problems? Mutations. In particular, it is recessive, deleterious alleles that are connected to problems from inbreeding. An allele is a version of a gene. Deleterious means that version has a negative effect on fitness. Recessive means that the negative effects of that allele are only seen when both copies of the gene are the deleterious version, a situation known as homozygous recessive.

Recall that we have defined inbreeding as the probability that both copies of a gene in an individual are identical by descent. If those identical by descent copies happen to be the recessive, deleterious version, then that individual will experience the deleterious effects. Therefore, inbreeding increases the probability that an individual will be affected by recessive, deleterious alleles.

For the sake of simplicity[7], let’s assume that god did a very solid job in the creation of humans and that the genomes of Adam and Eve contained no recessive, deleterious mutations[8]. Mutations that are transmitted to the next generation must occur in the germ line cells that produce gametes (i.e., sperm and eggs), which are isolated early on in development, minimizing the opportunity for mutations as cells divide to build the rest of the body.

How are rare, recessive, deleterious alleles generated? In humans, the germ line cells that will produce gametes (sperm and egg) are isolated early on in development, which greatly reduces the opportunity for mutations as cells divide like the rest of the body. These cells, however, do go through the process of meiosis to produce gametes. Mutations occur during meiosis due to errors in DNA copying or rearrangements between chromosome copies. As a result, individual gametes may contain new, recessive, deleterious alleles. These changes are random, rare, and occur independently for each resulting gamete, making it extremely unlikely that any two sperm or eggs will have the exact same mutations.

So, while Cain and Awan both might have carried recessive, deleterious alleles, it is highly improbable that either carried two copies of such an allele for any gene or that they carried the same recessive, deleterious allele as their sibling for any gene[9]. As a result, it is also extremely unlikely that the children of Cain and Awan would have had two copies of a recessive, deleterious allele for any gene, sparing them the physical consequences of their parents’ close family ties. Because Cain’s kids might have some of the same recessive, deleterious alleles as each other (inherited from meioses in Grandpa Adam or Grandma Eve), they would be well advised to wander at least as far as Uncle Seth’s house when it comes time to start their own families.

Oh, yeah, its also just an old story.

NOTES

There are two of them, folks. Check it out.

I’m focusing on Cain, but similar issues are presented when one considers Seth (Adam and Eve’s third son).

Most other major Christian groups do not consider the Book of Jubilees to be part of the Biblical canon.

“Seem to be” because it is not clear that it would be possible to realize such issues existed if they were universal amongst humans.

Usually around the tricky issue of first cousins.

Perhaps with a duplication to get that tricky, second X chromosome?

This analysis holds even if one does not assume that the creation was perfect and that the original humans did have recessive, deleterious mutations. It does break down if god intentionally created Adam and Eve with some of the same recessive, deleterious mutations (extremely unlikely by chance); but that would be a dick move.

As the myths indicate that the first humans were created as adults, I’m assuming that the cells of Adam’s rib did not go through mitosis during his non-existent development and, as a result, would contain no somatic mutations to pass on to Eve. One might, however, argue that hematopoetic stem cells in Adam’s bone marrow would have been dividing in order to maintain his supply of immune and blood cells, which could possible give Eve such mutations. One might have a good point, and one should perhaps write one’s own blog.

The only potential exception to this would be the extremely rare case of half-identical twins, where siblings share the same maternal genotype, but have different paternal genotypes. Such siblings could be of different sexes, but still share recessive, deleterious alleles inherited from their mother.

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